1. Field of the Invention
This invention relates to a process for preserving a patient's organ for transplantation which includes perfusing the organ with an aqueous solution that promotes anaerobic glycolysis by providing a high energy substrate, removes waste products from the organ by buffering, and maintains the energy production capacity of the organ.
This invention also relates to a process during cardioplegia in cardiac surgery which includes perfusing the heart with an aqueous solution that arrests the heart, promotes anaerobic glycolysis by providing a high energy substrate, removes waste products from the heart by buffering and maintains the energy production capacity of the heart until the heart is restarted by reestablishing the blood flow.
2. Background Information and Description of the Prior Art
It is well known by those skilled in the art to employ during transplantation of an organ and cardioplegia during cardiac surgery a solution that will preserve the organ during the complete interruption of its blood and oxygen supply. Generally, these solutions rely on substantially arresting the organ's metabolism with the use of chemicals and by employing temperatures of 4.degree. Centigrade and lower. This substantial slowing of the metabolism of the organ permits the energy stores in the organ at the time of harvesting to be consumed at a slower rate. Accordingly, the preservation time of these solutions is limited by the available energy stores present at the time of harvesting and the rate of their consumption. Organ preservation such as for example, preservation of the heart, is limited by the fact that currently available solutions are able only to safely preserve organs for very limited periods of time. For the heart, this time is generally less than six hours. This relatively short period of time severely limits the distance that these organs may be transported and imposes great demands upon the surgeon to complete the complex and delicate transplant surgery in an expeditious manner. Another disadvantage of these solutions is that they do not preserve the organ by promoting anaerobic glycolysis. For example, it is well known by those skilled in the art that prolonged myocardial preservation is limited by the heart's inability to maintain high energy stores and low intracellular calcium levels during ischemia. Anaerobic glycolysis, which is the only potential source of adenosine 5'-triphosphate (ATP) during ischemia, is inhibited by the accumulation of lactate and H.sup.+ in the myocytes. These waste products inhibit energy production by the organ while the organ is outside of the patient's body. As a result, ATP production during ischemia is inhibited. It is known by those skilled in the art that low ATP levels are associated with detrimental morphologic changes in the heart.
U.S. Pat. No. 4,415,556 discloses a protective solution for preventing ischemia damage to organs during transplantations. It discloses a solution that includes alpha-ketoglutarate to improve aerobic metabolism during perfusion. This patent states that alpha-ketoglutarate is able to lengthen the ischemia tolerance times. It discloses, however, that the ischemia tolerance time associated with the protective solution decreases as temperature rises from 5.degree. Centigrade to 35.degree. Centigrade.
U.S. Pat. No. 4,663,289 discloses a process and a solution for preservation of cells in a cell culture. It discloses an ionic balanced solution that normalizes the redox state of the cell wherein the solution contains a normal Na:Cl ratio. This patent includes L-histidine HCl.H.sub.2 O as a nutrient additive to the balanced salt mixture. The solution promotes aerobic metabolism by providing substrates for the mitochondria.
U.S. Pat. No. 4,920,044 discloses a hyperosmotic intracellular flush and storage solution for preserving an organ for transplantation. It states that the intracellular flush solution minimizes adenine nucleotide catabolism and post-preservation renal reperfusion injury. It also states that the intracellular flush solution comprises KH.sub.2 PO.sub.4, K.sub.2 HPO.sub.4, KCl, NaHCO.sub.3, KHCO.sub.3, mannitol, MgSO.sub.4, MgCl.sub.2, adenosine, allopurinol and verapamil. This patent utilizes the intracellular electrolyte flushing solution in combination with cold storage techniques for extending organ preservation.
U.S. Pat. No. 4,981,691 discloses an oxygenatable fluorocarbon nutrient cerebrospinal fluid containing electrolytes, lecithin, and amino acids. It states that the fluid may be employed for treating hypoxic-ischemic central nervous system tissue.
An article entitled "Effects of Low Extracellular Calcium on Cytosolic Calcium and Ischemic Contracture," Journal of Surgical Research, Vol. 49, pp. 252-255 (1990), and co-authored by E. Jimenez, M.D., et at., states that use of a low calcium cardiac arresting solution prior to ischemia improves the tolerance to ischemia.
del Nido, P., et at., "The Role of Cardioplegic Solution Buffering in Myocardial Protection", The Journal of Thoracic and Cardiovascular Surgery, Vol. 89, No. 5, pp. 689-699 (1985), discloses that histidine improves post-ischemic recovery of cardiac function and that zero calcium concentration in combination with a low potassium concentration is important for organ preservation.
Transplantation Art SU 878-297 teaches a heart perfusion aqueous solution which contains water, lidocaine, glucose, mannitol and phosphate.
Qayumi et al., "Preservation Techniques for Heart Transplantation: Comparison of Hypothermic Storage and Hypothermic Perfusion," Journal of Heart-Lung Transplant, Vol. 10, No. 4., pp. 518-526 (1991), discloses a heart perfusion solution which comprises mannitol, glucose, insulin and sodium.
In spite of the prior art disclosures, there remains a very real and substantial need for a process and aqueous solution for organ preservation and cardioplegia that promotes anaerobic glycolysis by providing a high energy substrate, removes waste products from the organ by buffering and maintains the energy production capacity of the organ.